The carbostyril derivatives represented by the general formula (I) and process for producing the same are described in Japanese Patent Publication No. 10 63-35623, the usefulness of carbostyril derivatives as anti-gastric ulcer agents is described in Japanese Patent Application Kokai (Laid-open) No. 3-74329, and processes for producing those carbostyril derivatives having optical activities are described in Japanese Patent Application Kokai (Laid-open) No. 3-145468.
Further, the inhibitory effect of carbostyril derivatives of the present invention on reactive oxygen metabolites is described in Japan. J. Pharmacol., Vol. 49, pp. 441-448 (1969), and the protectability of gastric mucous membrane by carbostyril derivatives of the present invention is described in Folia Pharmacol. Japon., Vol. 97, pp. 371-380 (1991).
Furthermore, the usefulness of carbostyril derivatives as agents for curing diabetes mellitus is described in International Publication No. WO 92/21342, the usefulness of carbostyril derivatives as agents for protecting the intestinal mucosa from disorders is described in International Publication No. WO 94/12182, and the usefulness of carbostyril derivatives as agents for inhibiting the reduction in secretion of somato-statin is described in International Publication No. WO 93/24043.
"Dry eye" symptom (xerophthalmia) is a pathogenic state (pathema) of the eye in which the surface of the eye cannot be maintained to normal condition due to a shortage of the amount of tears. Furthermore, the mucous membranes (the epithelia of the cornea and conjuctiva) on the surface of the eye may be caused not only by an abnormal shortage of the amount of tears, but also by an abnormal nature of tears [Cf. DORAI-AI (dry eye), page 11, by Kazuo TSUBOTA, published from NIPPON-HYORONSHA]. In addition to the above, such dry eye symptoms may be observed in case of Sjogren's syndrome with abnormal states (the amount and nature) of tears. Also, there have been known that the dry eye symptom may be occurred in the end-stage of Stevens-Johnson syndrome and observed that the cornea and conjuctiva are injured.
Tear fluid (lacrima) is a very thin liquid layer having 7 .mu.m in thickness, which covers the outmost (extima) layer of the front of eye, and having trilaminar structure consisting of lipid layer, aqueous layer and mucoid layer. The lipid layer being existed on the outmost surface layer of the tear fluid is an oily film, which is produced and secreted mainly from the meibomian glands located in periphery of the eyelids, and covers all over the aqueous layer. The lipid layer is considered to have the function for preventing evaporation of water from the aqueous layer. The aqueous layer is a portion of so-called "tears" which occupies the most thickness of the tear fluid layer, and 98% of the constituent thereof is water. A pathogenic state in decreasing of the amount of this aqueous layer is so-called as "dry eye" symptom. The mucoid layer covers the hydrophobic surface of the epithelium of the cornea, this mucoid layer changes the hydrophobic surface of the epithelium of the cornea to hydrophilic nature to maintains and extends the aqueous layer in the tear fluid, so that the aqueous layer can be able to maintain on the surface of the epithelium of the cornea. Cells related to producing said mucoid layer are goblet cells being contained in the conjuctiva.
As explained above, the tear fluid which may cause directly to introduce the "dry eye" symptom is involved in various tissue cells. Also the concept of "dry eye" symptom is complicated, so that a common type of eye drop preparation can only gives a temporary medical measure, thus at the present stage fundamental method for medical treatment of the "dry eye" symptom have not been found yet. So that new method and new agent for curing the "dry eye" symptom have been eagerly expected.